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Downregulation of Adiponectin/AdipoR2 is Associated with Steatohepatitis in Obese Mice

  • 2008 SSAT Quickshot Presentation
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

Recent evidence suggests that obesity is associated with hypo-adiponectinmia and chronic inflammation. Adiponectin regulates fat storage, energy expenditure, and inflammation. We propose that high fat diet induces steatohepatitis, reduces serum adiponectin, and liver adiponectin receptors.

Methods

A 4-week-old C57BL male mice were fed high fat diet (n = 8) or regular chow (control; n = 6) for 7 weeks. Body weight, liver weight, and serum adiponectin were measured. Liver sections were stained with hematoxylin and eosin and oil red for fat content. Liver homogenates were used for protein (immunoblotting) and mRNA (reverse transcription PCR) of Toll-like receptor 4 (TLR4), tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, sterol regulatory element-binding proteins (SREBP)-1c, and adiponectin receptors (AdipoR1/AdipoR2) in addition to nuclear phorsphorylated p65NF-κB. Gels were quantified using densitometry; t test was used, and p < 0.05 was significant.

Results

High fat diet increased body (50%) and liver weight (33%), as well as hepatocyte fat content and ballooning. Mice fed high fat diet exhibited reduced serum adiponectin and liver AdipoR2. High fat diet increased hepatic levels of SREBP-1c, TLR4, TNF-α, and IL-6 protein and mRNA and increased activation of p65NF-κB.

Conclusions

Diet-induced liver steatosis is associated with increased lipogensis, upregulation of pro-inflammatory cytokines, and transcription factors as well as downregulation of AdipoR2. Reduction in serum adiponectin suggests that adiponectin signaling may be the crosslink between high fat diet, hepatic inflammation, and nonalcoholic fatty liver disease.

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Author information

Authors and Affiliations

  1. Department of Surgery, University of South Florida, Tampa, FL, USA

    Yanhua Peng, Drew Rideout, Steven Rakita & Michel M. Murr

  2. Department of Endocrinology, University of South Florida, Tampa, FL, USA

    Mini Sajan & Robert Farese

  3. Department of Pharmacology, University of South Florida, Tampa, FL, USA

    Min You

  4. Tampa General Hospital, University of South Florida, P.O. Box 1289, Tampa, FL, 33601, USA

    Michel M. Murr

Authors
  1. Yanhua Peng
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  2. Drew Rideout
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  3. Steven Rakita
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  4. Mini Sajan
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  5. Robert Farese
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  6. Min You
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  7. Michel M. Murr
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Corresponding author

Correspondence to Michel M. Murr.

Additional information

This work was support by the VA Merit Award (MM), NIH R01 AA013623-06, AA015951-03 (MY), NIH R01 DK065969-05, and VA Merit Award (RF).

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Peng, Y., Rideout, D., Rakita, S. et al. Downregulation of Adiponectin/AdipoR2 is Associated with Steatohepatitis in Obese Mice. J Gastrointest Surg 13, 2043–2049 (2009). https://doi.org/10.1007/s11605-009-1032-2

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  • DOI: https://doi.org/10.1007/s11605-009-1032-2

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